Full Research Project 1: Survivorship Care Physical Activity Initiative to Reduce Disparities in HRQOL for Prostate Cancer Survivors (RELate Study) SUMMARY The late effects of prostate cancer (PCa) treatment can lead to unique physical and psychosocial issues that impact their long-term health-related quality of life (HRQOL). Increased physical activity (PA) is a modifiable risk factor which may be targeted to address PCa survivorship-related treatment outcomes and lifestyle behaviors. Increased PA may have greatest impact on outcomes for African-ancestry (AA) PCa survivors, who tend to have lower HRQOL and overall survival, and in whom factors such as a lack of exercise, poor diet, and rates of obesity are most prevalent. While it is well-known that exercise can improve prognosis among cancer survivors, little is known about the bio-behavioral mechanisms and pathways through which PA may improve HRQOL and increase overall survival. Advanced glycation endproducts (AGEs) are reactive metabolites produced during normal metabolism as well as the oxidation of biological macromolecules. Lifestyle factors such as a sedentary lifestyle, poor diet, and obesity increase AGE levels in the body. The investigators hypothesize that in a randomized trial of a human PA/dietary intervention with PCa survivors previously diagnosed with Stage I-III PCa (n=120), lower AGE levels will correlate with improved HRQOL, and will lead to differential changes in immune response between AA and European American (EA) trial participants. The investigators further hypothesize that in a mouse model intervention, the mechanistic implications of lifestyle- associated AGEs to tumor-associated immune response and tumor growth and/or progression will mimic those found in human models. Aim 1 is to complete a 1-year, 2-arm (intervention vs usual care) randomized PA/dietary intervention in men diagnosed with stage I-III PCa (co-led by Dr. M. Ahmed, SCSU and Dr. D. Turner, MUSC-HCC). Aim 2 is to evaluate the effect of lifestyle intervention on PA and diet, and define their relationship with AGEs, AGEs pre-cursors, and HRQOL in men diagnosed with stage I-III PCa (led by Dr. Ahmed, SCSU). Aim 3 is to use a spontaneous PCa lifestyle mouse model to define the role of AGE-RAGE signaling to immune-cell phenotypes and tumor progression (led by Dr. Turner, MUSC-HCC). The results could lead to innovative insights for pharmacologic and lifestyle adjustment, and could identify protective factors that may underlie observed differences in PCa treatment outcomes between AA and EA men. This project is synergistically related to the other research projects included in this application